Abstract
ObjectiveThe pathogenic mechanism of anti-tuberculosis (anti-TB) drug-induced hepatitis is associated with drug metabolizing enzymes. No tagging single-nucleotide polymorphisms (tSNPs) of cytochrome P450 2E1(CYP2E1) in the risk of anti-TB drug-induced hepatitis have been reported. The present study was aimed at exploring the role of tSNPs in CYP2E1 gene in a population-based anti-TB treatment cohort.Methods and DesignA nested case-control study was designed. Each hepatitis case was 14 matched with controls by age, gender, treatment history, disease severity and drug dosage. The tSNPs were selected by using Haploview 4.2 based on the HapMap database of Han Chinese in Beijing, and detected by using TaqMan allelic discrimination technology.ResultsEighty-nine anti-TB drug-induced hepatitis cases and 356 controls were included in this study. 6 tSNPs (rs2031920, rs2070672, rs915908, rs8192775, rs2515641, rs2515644) were genotyped and minor allele frequencies of these tSNPs were 21.9%, 23.0%, 19.1%, 23.6%, 20.8% and 44.4% in the cases and 20.9%, 22.7%, 18.9%, 23.2%, 18.2% and 43.2% in the controls, respectively. No significant difference was observed in genotypes or allele frequencies of the 6 tSNPs between case group and control group, and neither of haplotypes in block 1 nor in block 2 was significantly associated with the development of hepatitis.ConclusionBased on the Chinese anti-TB treatment cohort, we did not find a statistically significant association between genetic polymorphisms of CYP2E1 and the risk of anti-TB drug-induced hepatitis. None of the haplotypes showed a significant association with the development of hepatitis in Chinese TB population.
Highlights
Tuberculosis (TB) remains a major global health problem with estimated 8.8 million incident cases and 1.45 million deaths globally in 2010, most of these occurring in developing countries [1]
Eighty-nine anti-TB drug-induced hepatitis cases and 356 controls were included in this study. 6 tagging single-nucleotide polymorphisms (tSNPs) were genotyped and minor allele frequencies of these tSNPs were 21.9%, 23.0%, 19.1%, 23.6%, 20.8% and 44.4% in the cases and 20.9%, 22.7%, 18.9%, 23.2%, 18.2% and 43.2% in the controls, respectively
No significant difference was observed in genotypes or allele frequencies of the 6 tSNPs between case group and control group, and neither of haplotypes in block 1 nor in block 2 was significantly associated with the development of hepatitis
Summary
Tuberculosis (TB) remains a major global health problem with estimated 8.8 million incident cases and 1.45 million deaths globally in 2010, most of these occurring in developing countries [1]. Guidelines recommend a drug combination regimen, including isoniazid (INH), rifampin (RIF), ethambutol (EMB), pyrazinamide (PZA) and streptomycin (SM) as the first-line agents [2,3]. These drugs have ability to control and kill Mycobacterium tuberculosis effectively, but may cause various adverse effects, including liver injury, skin reactions, and gastrointestinal or neurological disorders [4,5]. Anti-TB drug-induced hepatitis is one of the serious adverse drug reactions, which often impedes scheduled treatment and cure [6]. Anti-TB drug-induced hepatitis encompasses a wide spectrum of liver injury, ranging from asymptomatic minimal elevation of liver enzymes to acute liver failure, and often leads to death or liver transplantation [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
